title: Synthesis and biological evaluation of aminobenzimidazole derivatives with a phenylcyclohexyl acetic acid group as anti-obesity and anti-diabetic agents.
abstract: A series of benzimidazole derivatives with a phenylcyclohexyl acetic acid group as DGAT-1 inhibitors was developed. Among the benzimidazole series, compound 5k showed submicromolar in vitro activity toward human and mouse DGAT-1, good selectivity toward DGAT-2, human liver metabolic stability, and pharmacokinetic (PK) and safety profiles such as hERG, CYP and acute toxicity. Additionally, 5k showed good in vivo efficacy in 4weeks study with DIO mouse model.
authors.affiliation: Drug Discovery Division, Korea Research Institute of Chemical Technology, Daejeon 305-600, Republic of Korea.
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Kwak
authors.forename: Yu Mi
authors.initials: YM
authors.lastname: Pyun
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Haushabhau S
authors.initials: HS
authors.lastname: Pagire
authors.forename: Ki Young
authors.initials: KY
authors.lastname: Kim
authors.forename: Kwang Rok
authors.initials: KR
authors.lastname: Kim
authors.forename: Sang Dal
authors.initials: SD
authors.lastname: Rhee
authors.forename: Won Hoon
authors.initials: WH
authors.lastname: Jung
authors.forename: Jin Sook
authors.initials: JS
authors.lastname: Song
authors.forename: Myung Ae
authors.initials: MA
authors.lastname: Bae
authors.forename: Duck Hyung
authors.initials: DH
authors.lastname: Lee
authors.forename: Jin Hee
authors.initials: JH
authors.lastname: Ahn
mesh_terms: D019342:Acetic Acid / Q000737:chemistry*; D000818:Animals; D019440:Anti-Obesity Agents / Q000138:chemical synthesis / Q000494:pharmacology; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002478:Cells, Cultured; D003500:Cyclization; D003920:Diabetes Mellitus / Q000188:drug therapy; D004195:Disease Models, Animal; D006801:Humans; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D008099:Liver / Q000187:drug effects; D051379:Mice; D015394:Molecular Structure; D009765:Obesity / Q000188:drug therapy
chemical_list: D019440:Anti-Obesity Agents; D001562:Benzimidazoles; D007004:Hypoglycemic Agents; C027391:2-aminobenzimidazole; D019342:Acetic Acid
keywords: Aminobenzimidazole; DGAT-1; Diabetes; Diacylglycerol acyltransferase-1; Obesity; TG; Triglycerides